The long-term objective of the proposed studies it to understand the molecular properties of proteins involved in quenching and restoration of the phototransduction cascade. Among sensory systems, vision holds a privileged position, with the ability to accurately analyze objects, distances, and colors. The light signal captured by photo-receptor cells triggers a cascade of chemical reactions, called phototransduction, that ultimately generates a neuronal signal. The goal of my research is to understand the biochemical basis underlying the mechanism of rhodopsin inactivation and restoration of the cGMP level. Knowledge about phototransduction in the retina, a system with great experimental advantages, will improve further understanding of similar events in hormonal signaling, cellular communication and immune regulation, and provide baseline information for further studies of retinal disease processes. The planned experiments are: (i) to elucidate the mechanism of rhodopsin phosphorylation by rhodopsin kinase (RK) and how RK is activated and regulated; (ii) to investigate the kinetics of rhodopsin phosphorylation- in particular to identify the sites of phosphorylation on the rhodopsin molecule in the presence of regulatory proteins; (iii) to identify and characterize the functional regions of RK; and finally, (iv) to explain the mechanism of guanylate cyclase regulation, specifically, modulation of cyclase activity by calcium.